Original Article Quantitative analysis of iris parameters in keratoconus patients using optical coherence tomography Uso de tomografia de coerência óptica na análise quantitativa dos parâmetros irianos em pacientes com ceratocone GUSTAVO BONFADINI1,2,3, KARUN ARORA4, LUCAS M. VIANNA1,3,5, MAURO CAMPOS3, DAVID FRIEDMAN4,6, BEATRIZ MUÑOZ4,6, ALBERT S JUN1 ABSTRACT RESUMO Purpose: To investigate the relationship between quantitative iris parameters Objetivo: Investigar a relação entre os parâmetros quantitativos irianos e a presença and the presence of keratoconus. de ceratocone. Methods: Cross-sectional observational study that included 15 affected eyes of Métodos: Estudo observacional transversal com quinze olhos de 15 pacientes com 15 patients with keratoconus and 26 eyes of 26 normal age- and sex-matched ceratocone e 26 olhos de 26 indivíduos normais, pareados por idade e gênero. Parâ- controls. Iris parameters (area, thickness, and pupil diameter) of affected and metros da íris (área, espessura e diâmetro da pupila) de olhos com ceratocone e olhos unaffected eyes were measured under standardized light and dark conditions sem ceratocone foram medidos usando tomografia de coerência óptica do segmento using anterior segment optical coherence tomography (AS-OCT). To identify opti- anterior (AS-OCT), em condições padronizadas de alta luminosidade e ambiente mal iris thickness cutoff points to maximize the sensitivity and specificity when escuro. Com o objetivo de maximizar a sensibilidade, especificidade e identificar o discriminating keratoconus eyes from normal eyes, the analysis included the use melhor ponto de corte na diferenciação entre ceratocone e indivíduos normais, foi of receiver operating characteristic (ROC) curves. realizada a análise quantitativa da curva característica operacional do receptor (ROC) Results: Iris thickness and area were lower in keratoconus eyes than in normal dos parâmetros de espessura da íris. eyes. The mean thickness at the pupillary margin under both light and dark condi- Resultados: A área e espessura da íris estavam reduzidas nos olhos de pacientes com tions was found to be the best parameter for discriminating normal patients from ceratocone. Observamos que o melhor parâmetro para discriminar indivíduos normais keratoconus patients. Diagnostic performance was assessed by the area under the de pacientes com ceratocone foi a espessura média na margem pupilar, tanto em ROC curve (AROC), which had a value of 0.8256 with 80.0% sensitivity and 84.6% condições de alta luminosidade quanto em ambiente escuro. O desempenho diagnós- specificity, using a cutoff of 0.4125 mm. The sensitivity increased to 86.7% when tico deste parâmetro foi avaliado pela análise quantitativa da área sob a curva ROC a cutoff of 0.4700 mm was used. (AROC), mostrando AROC de 0,8256, com sensibilidade de 80,0% e especificidade de Conclusions: In our sample, iris thickness was lower in keratoconus eyes than 84,6% usando um ponto de corte de 0,4125 milímetros de espessura da íris. A sensibi- in normal eyes. These results suggest that tomographic parameters may provide lidade aumentou para 86,7%, com um corte de 0,4700 milímetros de espessura da íris. novel adjunct approaches for keratoconus screening. Conclusões: Na amostra deste estudo, a espessura da íris demostrou-se reduzida nos olhos com ceratocone. Estes resultados sugerem que os parâmetros tomográficos podem proporcionar novas informações no auxilio da triagem de pacientes com ceratocone. Keywords: Tomography, optical coherence; Iris; Keratoconus; Cornea; Dilatation Descritores: Tomografia de coerência óptica; Íris; Ceratocone; Córnea; Dilatação pa­­ pathologic; ROC curve tológica; Curva ROC INTRODUCTION plantation has inherent intra- and postoperative risks, and the surgery Keratoconus is traditionally described as a noninflammatory ectatic significantly affects the patient’s quality of life during the surgical re- disorder of the cornea characterized by progressive thinning, steepe- covery phase and beyond, with lost work time and often permanent ning, and apical protrusion. These corneal changes induce irregular changes in vision and lifestyle. astigmatism and myopic shift, causing impairment of vision. The The diagnosis of moderate-to-advanced keratoconus is not diffi- incidence of keratoconus in the general population is estimated to be cult because of the presence of irregular astigmatism on corneal approximately 1 in 2000(1). Keratoconus is the second most frequent topography and the development of classical clinical signs. However, indication for corneal transplantation, accounting for approximately identifying subclinical forms of the disease in patients with normal 12% of corneal transplants performed in the United States(2) and is best-corrected visual acuity (BCVA) and minimum or no clinical signs one of the main indications of keratoplasty in Brazil(3). Corneal trans- is challenging. The identification of very early forms of keratoconus Submitted for publication: February 23, 2015 Funding: No specific financial support was available for this study. Accepted for publication: July 6, 2015 Disclosure of potential conflicts of interest: None of the authors have any potential conflict of 1 Cornea and Anterior Segment Service, The Wilmer Eye Institute, Johns Hopkins School of Medicine, interest to disclosure. Baltimore, MD, USA. 2 Corresponding author: Albert S. Jun. 400 N. Broadway, Smith Building 5011 - Baltimore, MD Rio de Janeiro Eye Bank (INTO), Rio de Janeiro, RJ, Brazil. 21231 - E-mail: [email protected] 3 Department of Ophthalmology and Visual Sciences, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. Approved by the following research ethics committee: Institutional Review Boards (IRB): 4 Dana Center for Preventive Ophthalmology, The Wilmer Eye Institute, Johns Hopkins School of No 00051452. Johns Hopkins School of Medicine, Baltimore, MD, USA. Medicine, Baltimore, MD, USA. 5 Universidade Estadual do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. 6 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. http://dx.doi.org/10.5935/0004-2749.20150080 Arq Bras Oftalmol. 2015;78(5):305-9 305 Quantitative analysis of iris parameters in keratoconus patients using optical coherence tomography or forme fruste keratoconus relies on topographic data and subjec- Table 1. Participant characteristics tive clinical impression. Thus, more objective parameters are needed Keratoconus Controls when evaluating patients with forme fruste keratoconus, such as n=15 n=26 those with asymmetric or unilateral keratoconus, family members Parameter Mean (SD) Mean (SD) P-value of keratoconus patients, and patients undergoing evaluation for re- fractive surgery. Demographics Corneal tomography provides three-dimensional reconstruction Age in years 38.0 (11.4) 34.1 (10.0) 0.260 of the cornea, enabling evaluation of the anterior and posterior corneal Male 77.7% 46.2% 0.200 surfaces and creation of a corneal pachymetric (thickness) and topo- Race graphic map. Commercially available corneal tomography systems White 46.7% 61.5% *Fisher’s exact that use a rotating Scheimpflug cameras have been proposed to 0.004 help identify forme fruste keratoconus(4), and high-speed anterior Asian 00.0% 19.2% segment optical coherence tomography has been shown to have Black 46.7% 03.9% good repeatability and reproducibility with ocular structures and iris Hispanic 06.7% 07.7% area measurements(5-9). Refraction In a subset of keratoconus patients undergoing penetrating kera- toplasty (PKP), we have observed that the iris can show a tendency to Sphere -3.5 (2.1) -5.2 (3.3) 0.080 prolapse toward the incisions and be less responsive to pharmacolo- Cylinder -3.0 (2.4) -0.7 (0.8) 0.030 gical agents. Urrets-Zavalia syndrome, an uncommon postoperative Spherical equivalent -2.0 (2.4) -4.8 (3.0) 0.004 complication of PKP, has also been associated with keratoconus, which SD= standard deviation. suggests an intrinsic abnormality in irises with this disease(10). Others *= Fisher’s exact test was used to compare the racial distribution between keratoconus have described an association between keratoconus and floppy patients and controls. eyelids(11,12). Thus, multiple lines of evidence indicate extracorneal ma­­ nifestations of keratoconus involving the iris and/or the periocular skin and connective tissues. In this report, we describe the novel use of AS-OCT to determine iris parameters for discriminating between normal individuals and AS-OCT IMAGE ACQUISITION keratoconus patients. The Visante OCT used in this study has axial and transverse image resolution up to 18 and 60 μm, respectively. All participants were METHODS imaged in the enhanced anterior segment single mode to acquire an image centered over the pupil on the horizontal meridian, and SUBJECTS proper eye alignment was indicated by an interference beam along Approval was granted by the Johns Hopkins Institutional Review the visual axis (scan length 16 mm; 256 A-scans). No pharmacologic Board for this study. All study procedures adhered to the tenets of agents were applied to the eye prior to imaging. The inset image the Declaration of Helsinki. This was a prospective, cross-sectional, on the monitor screen was used as a guide to ensure that there was clinic-based evaluation of patients who presented to the cornea minimal eye movement and no blinking during imaging. service at the Wilmer Eye Institute. The study population consisted AS-OCT imaging of the study eye